2-Methyl-1H-indole-5-carbonitrile → 3-Methyl-1H-indole-5-carbonitrile

Participants

Reaction Conditions

Reaction Steps

Splitting off of the trimethylsilyl groups was carried out in two stages. The mixture of the nitriles from the previous stage (5.15 g, crude product) was dissolved in tetrahydrofuran (60 ml), tetrabutylammonium fluoride×3H2O (5.58 g, 17.7 mmol) was added and the mixture was stirred at room temperature for 4 h. Water (150 ml) was added to the reaction mixture and the mixture was stirred for 10 min. After the addition of diethyl ether (50 ml), the phases were separated. The aqueous phase was extracted with diethyl ether (3×150 ml). The combined organic phases were dried and concentrated. The residue was a brown oil (3.4 g), which was separated by chromatography [silica gel 60 (170 g); ethyl acetate/cyclohexane (1:10, 1,600 ml), ethyl acetate/cyclohexane (1:4, 500 ml)]. 3-Methyl-2-trimethylsilanyl-1H-indole-5-carbonitrile was obtained by this procedure as a beige-coloured solid in a yield of 60% (1.92 g) with a melting point of 128-131° C. A product mixture of the indole 3-methyl-1H-indole-5-carbonitrile and 2-methyl-1H-indole-5-carbonitrile (264 mg), which were present virtually in a ratio of 1:1, was furthermore isolated. The silyl compound 3-Methyl-2-trimethylsilanyl-1H-indole-5-carbonitrile (1.9 g, 8.32 mmol) was dissolved in tetrahydrofuran (60 ml) and the solution was heated at 60° C. for 2 h. The mixture was then concentrated, water (150 ml) was added and the mixture was stirred for 10 min. After addition of diethyl ether (100 ml), the phases were separated. The aqueous phase was extracted with diethyl ether (2×50 ml). The organic phases were dried and concentrated. 3-Methyl-1H-indole-5-carbonitrile (Ind-6) was obtained by this procedure as a beige-coloured solid in a yield of 99% (1.33 g) with a melting point of 110-112° C.

Provenance & Evidence